AdvanCell’s 212Pb-ADVC001 demonstrates encouraging safety and compelling anti-tumor activity in Phase 1b in prostate cancer

Results from the TheraPb Phase 1b dose escalation presented at ESMO 2025 show a promising therapeutic index for 212Pb-ADVC001 in patients with metastatic castration-resistant prostate cancer (mCRPC) No dose-limiting toxicities and no treatment-related serious adverse events observed Xerostomia predominantly Grade 1 80% PSA50 response at doses ≥ 160 MBq 100% objective response rate (ORR) in patients with RECIST-measurable lesions, including two complete responses (CRs) The data represent the first clinical trial results for a Lead-212 (212Pb)-based PSMA-targeted radioligand therapy and highlight the potential of 212Pb-ADVC001 to enhance therapeutic options for patients with prostate cancer Phase 2 expansion will evaluate 160 MBq and 200 MBq of 212Pb-ADVC001 using a randomized multi-dose-response design and adaptive dosing strategies to optimize clinical outcomes in three indications: mCRPC (chemo-naïve, and post-177Lu-PSMA) and hormone-sensitive prostate cancer (mHSPC)

AdvanCell, a clinical-stage radiopharmaceutical company developing innovative targeted alpha therapies for cancer, presented results from the Phase 1b dose escalation of the TheraPb Phase 1/2 clinical trial (NCT05720130) at the European Society for Medical Oncology (ESMO) 2025 congress. The presentation featured the first clinical results of 212Pb-ADVC001, a novel Lead-212-based PSMA-targeted alpha therapy in mCRPC.

“We are very encouraged by the completion of the treatment period of our Phase 1 trial, which has demonstrated a favorable safety profile and compelling anti-tumor activity for 212Pb-ADVC001," said Anna Karmann, MD PhD, Chief Medical Officer of AdvanCell. “These results underscore the potential of our therapy to meaningfully impact patients’ lives and advance treatment options in metastatic prostate cancer. I want to sincerely thank the investigators, clinical teams, and most importantly the patients and their families, whose commitment has made this important milestone possible.”

“The TheraPb Phase 1 trial of 212Pb-ADVC001 marks a pivotal step forward in the evolution of PSMA-targeted radioligand therapy,” said Aaron Hansen, MD, Principal Investigator at Princess Alexandra Hospital. “We’ve observed a compelling therapeutic index, including marked reductions in tumor volume and PSA, alongside a promising safety and dosimetry profile. The ability to administer alpha therapy easily and efficiently in an outpatient setting is a major clinical advantage. I am excited about the potential of 212Pb-ADVC001 to redefine treatment for patients with prostate cancer.”

Oliver Sartor, MD, Director of the Transformational Prostate Cancer Research Center at East Jefferson General Hospital, remarked, “The results from this Phase 1 trial demonstrate a strong efficacy signal combined with an excellent safety profile. This is an extremely promising step forward in delivering targeted alpha therapy to patients with prostate cancer.”

The abstract submitted to ESMO was based on a data cut-off as of May 9, 2025. The presentation at ESMO includes updated safety and efficacy data from all seven treatment cohorts as of an October 2, 2025 cut-off.

The TheraPb Phase 1b dose escalation study enrolled 22 patients with mCRPC. Escalating doses of 60–200 MBq of 212Pb-ADVC001 were administered at prespecified schedules every 6, 4, 2 and 1 week(s) for up to six cycles. After cohort 1, six subsequent treatment cohorts were enrolled within ten months.

TheraPb Phase 1b dose escalation results as of October 2, 2025 cut-off:

Encouraging safety and tolerability

• No dose-limiting toxicities, treatment-related serious adverse events or treatment-related adverse events leading to dose modification or treatment discontinuation
• Xerostomia predominantly Grade 1, with evidence of reversibility

Promising anti-tumor activity

• 80% PSA50 biochemical response at therapeutic doses ≥ 160 MBq
• 100% ORR in patients with RECIST-measurable lesions, including two CRs
• PSA, imaging and clinical responses within weeks of treatment start

Favorable dosimetry and kinetics

• Low normal-organ radiation exposure that supports a dosing strategy beyond six cycles and enhanced dose intensity
• Fast clearance and no relevant metabolic breakdown

The data represent the first clinical trial results of a 212Pb-based PSMA therapy. The findings support the further development of 212Pb-ADVC001 and may offer a new reference point in the treatment landscape for metastatic prostate cancer, both within and beyond the PSMA-targeted class.

Phase 2 expansion will evaluate 160 MBq and 200 MBq of 212Pb-ADVC001 using a randomized multi-dose-response design and adaptive dosing strategies to optimize clinical outcomes in three indications: mCRPC (chemo-naïve, and post-177Lu-PSMA) and mHSPC.

The poster presentation is available on AdvanCell’s website at: AdvanCell ESMO 2025 Poster

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About the TheraPb trial

The TheraPb trial (NCT05720130) is a prospective, open-label Phase 1/2 dose-escalation and expansion study designed to determine the safety and tolerability of escalating doses of 212Pb-ADVC001 administered every 6, 4, 2 or 1 week(s) during the dose finding Phase 1b. The Phase 2 expansion will assess the efficacy and safety of 212Pb-ADVC001 at the recommended Phase 2 doses across three indications. The trial utilizes a randomized dose-response design and dose optimization elements to rigorously evaluate optimal dosing strategies of 212Pb-ADVC001 in PSMA-positive mCRPC and mHSPC.

About 212Pb-ADVC001

212Pb-ADVC001 is a proprietary and patented PSMA-targeting radioligand with optimized physicochemical properties and labelled with 212Pb, an alpha-emitting payload (radionuclide) with a high dose rate, short half-life (10.6 hours) and simple decay scheme. 212Pb-ADVC001 is designed to deliver radiation at a cellular level to more effectively kill prostate cancer cells while minimizing toxicity.

About AdvanCell

AdvanCell is a vertically integrated, clinical-stage radiopharmaceutical company dedicated to developing innovative cancer therapies that harness the power of targeted alpha-emitting radionuclides. By leveraging its proprietary Lead-212 platform, advanced and scalable manufacturing capabilities and world-class clinical development capabilities, AdvanCell aims to deliver novel treatments that improve outcomes for patients with cancer globally. For more information, visit www.advancell.com.au and follow us on LinkedIn.

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